Lecture 13: Evasion of Immune Responses Flashcards
What are the 3 ways a pathogen can evade a host’s immune response?
- antigenic variation
- latency
- subversion of host response/molecular mimicry
What is antigenic variation?
Pathogen displays new Ag that are not recognized by an immune response previously formed against this pathogen
T or F: Antigenic variation allows a pathogen to evade a new immune response launched by a host.
False: it allows them to evade PRE-FORMED memory immune responses
How many different serotypes does S. pneumonia have?
84
What is the significance of the ability for pathogens to have many serotypes? (In terms of host recognition/response
The host has to launch a new Ab response to each serotype in order to clear the infection. This allloews a single pathogen to infect the same person over and over again.
T or F: Serotypes of pathogens ensure that the pathogens (almost) always have a host.
True
What is the difference between antigenic drift and antigenic shift?
Antigenic drift results from slight changes in a pathogen’s antigenic determinants.
Whereas an antigenic shift causes a much larger/more radical change in the antigenic determinants.
Ag drift only requires an altered B cell response (T cell response is still viable) while Ag shift requires new B and T cell response to be launched
(if not completely new T cell response, a mostly new)
Identify the flowing as characteristic as belonging to either antigenic drift or shift:
Caused the H1N1 epidemic
shift
Identify the flowing as characteristic as belonging to either antigenic drift or shift:
Caused by mutation in pathogen’s genome
drift
Identify the flowing as characteristic as belonging to either antigenic drift or shift:
T cells response can still protect the host
drift
Identify the flowing as characteristic as belonging to either antigenic drift or shift:
Causes seasonal flu epidemics
drift
Identify the flowing as characteristic as belonging to either antigenic drift or shift:
When initially infected by a viral pathogen, NK cells are the only cells killing infected cells.
shift
Identify the flowing as characteristic as belonging to either antigenic drift or shift:
Caused by recombination of viral gene segments
shift
Identify the flowing as characteristic as belonging to either antigenic drift or shift:
Caused by recombination of viral gene segments
shift
Identify the flowing as characteristic as belonging to either antigenic drift or shift:
Results in a virus expressing a completely new hemagglutinin or neuraminidase
shift
Identify the flowing as characteristic as belonging to either antigenic drift or shift:
Requires a secondary non human host prior to infecting humans
shift
Identify the flowing as characteristic as belonging to either antigenic drift or shift:
Requires new T helper response
Shift
Describe the process of antigenic drift in the influenza virus.
A person has previously infected by a pathogen. Therefore this pathogen cannot infect his or her cells. This same pathogen acquires a mutation that produces a slightly altered hemagglutinin or neuraminidase. This “mutated” virus is not recognized by the person’s Ab response and is therefore able to infect his or her cells.
Describe the process of antigenic shift in the influenza virus.
An animal (such as a pig) becomes infected with 2 viruses of different animal origins (such as human and avian). The segmented genomes of these 2 viruses become shuffled and packaged together (in new combinations). This novel virus expresses hemagglutin or neuraminidase that is not recognized by a human’s T or B memory memory cells → infection!
Describe the antigenic variation that allows Trypanosome to evade a host’s immune system.
What the term for this mechanism?
Trypanosome has a cassette system of 1000s of genes that code for a variable surface glycoprotein (VSG) coat. The pathogen expresses a single VSG at a time, and once the host’s immune system has “successfully” killed the parasite, it switches VSGs. The host must then launch a new B (and T??) cell response allowing the parasite to replicate and thrive again. → many cyclical periods of trypanosome replication while evading host cell immune response
This is known as PROGRAMMED REARANGEMENT
What disease does trypanosome cause?
African sleeping sickeness: creates many immune complexes that are deposited in the vasculature → damage to the vasculature all over the body → damages neural tissue → death
Does the typical disease syndrome resulting from infection with a genetic drift variant differ from that caused by a genetic shift variant of Flu? Explain why or why not.
Yes. A genetic drift variant would cause a MILDER disease because of existing memory T cell responses in people that have been previously infected. The flu will be cleared much FASTER too.
What is a state adopted by viruses in which they have entered the cells but do not replicate.
Latency
FYI TB can exhibit latency, so I don’t think it is unique to viruses
Describe a latent virus (in general terms, not a specific type).
It infects a host cell and integrates its genome into the host genome. For a period of time, no pathogen proteins will be made (meaning there won’t be anything to present to T cells) or secreted (meaning there wont be anything to prime a B cell response). Once the virus becomes reactivated, viruses are made and secreted.
While a virus is latent, it does not cause the host cell to make or secrete viral proteins. How is this significant?
The virus goes undetected by the host’s immune system. When proteins that are made, they are packaged onto MHC to be presented to T cells. And when they are secreted, they B cell response is able to be primed. Since this is not happening, B and T cells are not activated against the virus
T or F: viruses in the latent phase can infect other hosts.
False. They can only infect once they have been reactivated
Describe the “cycle” the herpes virus uses to evade a host’s immune system.
- Once a virus infects an area of tissue (primary infection) it begins to replicate.
- Some of the viruses travel down neurons and into the trigeminal ganglion where the virus integrates into the host genome.
- It is now in the latency phase.
- Once the virus is reactivated (mechanism is not understood but stress and sunlight are though to trigger it) it travels back down the the same nerve to (usually) the primary site of infection and the cycle continues.
How does Varicella zoster virus evade a host’s immune system?
Latency
It is the virus that causes chickenpox/shingles and can be reactivated along ONE nerve pathway = why it is seem on one half of the body
What viruses inhibit humoral immune response? What mechanism do these viruses specifically use?
- Herpes simplex cytomegalovirus: encode FcR homologs that bind up Ab to interfered with phagocyte recognition or recognition of target cells for ADCC (by NK cells)
- Herpes simplex: encodes a complement receptor to block complement mediated effector pathways
- Vaccinia: complement control proteins to inhibit efficient complement activation of infected cell
What are 4 mechanisms that pathogens use to inhibit the inflammatory response? And give and example of a virus that does each
- chemokine receptor homolog: cytomegalovirus
- inhibition of adhesion molecules to block lymphocyte trafficking to infected cells: Epstein-Barr Virus
- TLR homologs to prevent inflam response elicited by cytokines/bac pathogens: Vaccinia
- soluble cytokine receptor to bind up cytokines/block them from having effect: Vaccinia
What pathogens block the Ag processing and presentation and how do they do this? (2)
- herpes simplex cytomegalovirus: upregulate INF-gamma –> inhibits MHC class I
- Herpes simplex: inhibit TAP –> no loading of peptides onto MHC class I
What virus immunosupresses the host and how does it do this?
Epstein Barr by making IL-10 homologs. IL-10 homolog binds IL-10 receptor –> anti-inflammatory response created
How does cytomegalovirus subvert immune responses?
- interfere with Ag processing and presentation onto MHC class I molecules by
- inhibiting TAP, blocking proteosome access to viral protein, retaining MHC class I in ER, downregulates MHC I expression
- Interferes with NK function by down regulating MIC protein expression and making MHC class I homologs
How does cytomegalovirus prevent Ag processing and presentation onto MHC class I molecules? (5)
inhibiting TAP blocking proteosome access to viral protein retaining MHC class I in ER down regulates MHC I expression destroys MHC class I
What is a superantigen? What is their significane?
protein that binds alpha chain of MHC I and Beta-chain of TCR to activate T cell to produce cytokines.
They can activate 2-20% of T cells in the human body–> cytokine storm –> pathogen can evade immune response but it often results in the death of the host
T or F: Superantigen binding to MHC and TCR is Ag specific.
False: it is not –> why so many T cells are able to be activated to cause a cytokine storm
TSS can be caused by the effects of a _______
superantigen
What are 2 examples of a superantigen?
SE and TSST-1
In what part of the world is HIV the most widespread?
Sub-Saharan Africa
What is integrase? Where is it found?
it is the enzyme that HIV uses to integrate into host genome and it is found inside the envelope
What type of genome does HIV have (DNA? RNA? ss? ds?
dsRNA
RNA pol lacks _____ which causes ______
proofreading abilities –> antigenic drift
T or F: HIV undergoes antigenic shift
False: antigenic drift
Explain why HIV is said to “efficiently” utilize its genome.
it uses all 3 reading frames and uses alternate splicing
How has HIV taken advantage of human behavior?
it is sexually transmitted and transmitted with shared needles
What cells does HIV target?
CD4 T cells
How does HIV enter host cells?
binds CD4 and chemokine receptor on T cell and viral envelope fuses with cell membrane and allows viral genome to enter cell
Describe the life cycle of HIV. (latency and activation)
Once the viral genome is in the cell…
Latency:
reverse transcriptase take dsRNA –> cDNA
–> cDNA enters nucleus
–> integrase inserts cDNA into host genome
Activation:
T cell activation induces some Tx of provirus (NfxB = Tx factor)
–> provirus transcripts are spliced and synthesized into Tat and Rev
–> tat amplifies Tx of viral RNA
–> rev increases transport of RNA into cytosol
–>Gag, Pol, and Env are made and assembled with viral RNA into virons
–> virons but from cell
What is the role of Tat?
early HIV protein that amolifies the Tx of vrial RNA
What is the role of Rev?
carries HIV RNA from the nucleus to the cytoplasm
Describe the immune response against HIV during the first few weeks of infection.
initally, the immune system makes a strong B and T cell mediated responses againsts HIV, but they do not clear the infection. After this, the virus enters the latency phase in which the immune system keep the virus at bay for a number of years
T or F: the immune response to HIV can help the virus evolve to better evade the immune system.
True
Ultimately, there is _______ with a decreased immune response due to depletion of _____
increased viremia
CD4 T cells
T or F: During the latency period, persons infected with HIV are symptomatic.
False
At what conc of CD4 T cells/microL can a person be classified as an AIDS patient.
200 CD4 T cells/ microL
AIDS is terminal and a patient with it is likely to die from ______
an opportunistic infection
What are the different ways that HIV evades the immune system?
- antigenic drift
- latency
- molecular mimicry (has Ag similar to atrocytes–> neurological issues)
- induction of acquired immunodeficiency
